2. Academic Validation
  3. NKG2A and circulating extracellular vesicles are key regulators of natural killer cell activity in prostate cancer after prostatectomy

NKG2A and circulating extracellular vesicles are key regulators of natural killer cell activity in prostate cancer after prostatectomy

  • Mol Oncol. 2023 Mar 17. doi: 10.1002/1878-0261.13422.
Yu-Chuan Lu 1 2,  Chen-Hsun Ho 3 4,  Jian-Hua Hong 2 5,  Ming-Chieh Kuo 6,  Yi-An Liao 2,  Fu-Shan Jaw 5,  Jason Chia-Hsien Cheng 7,  Chao-Yuan Huang 2,  Ko-Ping Chang 8,  Chung-Hsin Chen 2,  Jung-An Lin 9,  An Hsiao 9,  Hsiu-Ni Kung 9
Affiliations

Affiliations

  • 1 Department of Surgical Oncology, National Taiwan University Cancer Center and National Taiwan University College of Medicine, Taipei, Taiwan.
  • 2 Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
  • 3 Division of Urology, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
  • 4 School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
  • 5 Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
  • 6 Department of Urology, National Taiwan University Hospital, Yunlin Branch, National Taiwan University, College of Medicine, Taipei, Taiwan.
  • 7 Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
  • 8 Department of Pathology, National, Taiwan University Hospital.
  • 9 Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
PMID: 36931723 DOI: 10.1002/1878-0261.13422
Abstract

Extracellular vesicles (EVs) are an important regulatory factor for natural killer cell activity (NKA) in the tumor microenvironment. The relationship between circulating EVs in the peripheral blood and natural killer (NK) cells in prostate Cancer is unclear. This study aims to investigate the key regulators in the interaction between circulating EVs and NK cells in prostate Cancer patients before and after tumor removal. NK-cell characteristics were prospectively assessed in 79 patients treated with robot-assisted laparoscopic radical prostatectomy (RARP) preoperatively and postoperatively. Compared with healthy donors, the existence of prostate tumors increased the number of circulating EVs and altered ligand expression of EVs. Circulating EVs extracted from Cancer patients significantly decreased NKA of NK cells compared to those extracted from healthy donors. Upon treatment with an inhibiting antibody or small interfering RNA (siRNA), natural killer cell protein group 2A (NKG2A) was identified as the main NKA regulator in Cancer patients for accepting the signal from circulating EVs. After surgery, NKA was increased and NKG2A expression on NK cells was significantly reduced. The expression of ligands for NKG2D on EVs and the level of circulation EVs both significantly increased. With the decrease in NKG2A levels on NK cells and the increase in total NKG2D ligands on circulating EVs, which was increased postoperatively, both NKG2A on NK cells and NKG2D ligands on circulating exosomes are main regulators of NKA restoration after prostatectomy.

Keywords

NKG2A; Natural killer cell activity; circulating EVs; ligand alterations; prostate cancer; robotic-assisted radical prostatectomy.

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